This grant application proposes two randomized, double-blind, placebo-controlled trials to be performed in the Pediatric Heart Disease Clinical Research Network. Our shorter-term trial will study the efficacy and safety of pulse steroid therapy, when added to conventional therapy with intravenous gamma globulin (IVIG) plus aspirin, in treatment of acute Kawasaki disease. Patients will be randomly assigned to receive either methylprednisolone (IVMP), 30 mg/kg, plus conventional therapy (i.e., "IVMP plus IVIG") versus placebo plus conventional therapy ("IVIG alone"). Our first aim is to test the hypothesis that treatment of acute Kawasaki disease with IVMP plus IVIG is more effective than treatment with IVIG alone. Our primary efficacy outcome variables will be BSA-adjusted coronary artery dimensions (z-scores) for the proximal right, left main, and proximal left anterior descending coronary arteries; number of days of fever after completion of initial IVIG infusion; and C-reactive protein at 2 weeks after illness onset. Our second aim is to test the hypothesis that children treated with IMP plus IVIG will have fewer adverse effects than those treated with IVIG alone. Our primary safety outcome will be the prevalence of all adverse side effects. The structure of the study will allow us to explore and identify factors other than the two treatment strategies (e.g., immune gene polymorphisms) that relate to the occurrence of-coronary artery abnormalities. The KD trial will span less than two years from onset of enrollment to preliminary data. Our longer-term trial evaluates the efficacy of beta-blocker therapy in retarding progressive aortic root dilation and valvular aortic regurgitation in patients after the arterial switch operation (ASO). Patients will be randomly assigned to receive either propranolol (2-4 mg/kg/day) or placebo. Our first aim is to assess the effect of propranolol therapy on the rate of aortic root dilation after the ASO. The primary outcome variable is the change in aortic root size during two years of treatment, assessed as the aortic root diameter adjusted for body surface area (BSA). A second specific aim is to assess the incidence and magnitude of adverse effects of propranolol therapy. The primary end-point will be the change in the Physical Health Summary and Psychosocial Health Summary scores of the CHQ-50 at one and two years of therapy compared to pre-therapy. A third specific aim is to evaluate the role of collagen and fibrillin in the pathogenesis of aortic root dilation after the ASO by analyzing single nucleotide polymorphisms (SNPs) in candidate genes: fibrillin and Collagen types 3al, 5al, and 5a2 genes. The primary endpoint is the identification of SNPs that are significantly associated with severity of aortic root dilation. The ASO trial will involve an enrollment period of two years and a follow-up period of 2 years. Both trials are expected to yield information important to clinical practice.